2017-08-23 I S R T R E A T I N G V I R A L I N F E C T I O N S T H R O U G H V I R U S E L I M I N A T I O N © 1
Immune System Regulation Holding ABwww.israb.se
2017-08-23 I S R T R E A T I N G V I R A L I N F E C T I O N S T H R O U G H V I R U S E L I M I N A T I O N © 2
ISR Holding AB – At a Glance
▪ Headquartered in Stockholm, Sweden
▪ Listed on Nasdaq First North in Stockholm
▪ R&D facilities at Karolinska Institute, Solna, Sweden
▪ A broad product portfolio and a strong patent base
▪ PoC Phase II data and several lead drug candidates in preclinical phase
▪ Strong R&D engine and partnership in UK
Capital raised until Q4 2016, 51 MSEK - High level of cost effectiveness
2012 20162014
2016:
▪ SEK 40 million
new issue
2015:
▪ SEK 11 million new issue
▪ Mikael Brönnegård
appointed CEO
▪ ISR Holding AB is founded
as a separate company
2012:
▪ ISR AB is established under
the umbrella of ITH AB (KI)
2017 2019
2013-2014:
▪ Phase IIa clinical trial
in South Africa
2016-2017:
▪ CTA submission to
MCC South Africa
2017 milestones
new chemistry
▪ IND ISR49
▪ IND ISR50
2018 and beyond:
▪ Launch of the first HIV
indication with GnRH
▪ Start of clinical trials
with ISR49 and ISR50
2017:
▪ Three patent filed ISR49
▪ Four patent filed ISR50
▪ One patent filed based on
CT ISR001 (Phase IIa)
2017-2018 milestone
clinical program
▪ Expected start of Phase
IIb (ISR48)
▪ Start of Phase IIa in
Sweden (ART+ISR48)
2012:
▪ Initial observation in cats that GnRH
might be a potential regulator of the
immune system
2018
24th Mars 2017
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Clinical challenges in patients with life-threateningvirus infections
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The Immune System – Target for Drug Development
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A new era in medicine - Immunotherapy
Immunotherapy and viral diseaseNew and more aggressive viruses
Immunotherapy and cancerGrowing elderly population
Immunotherapy and bacterial diseaseResistance to antibiotics
Offers solutions to lifethreatening diseases
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Primary Diseases for ISR´s Products
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Market Review and Competitive Analysis
▪ HIV continues to be a major global public healthissue with a significant burden of disease
▪ There is no cure for HIV infection
▪ New and more effective therapies are still needed
▪ No alternative treatment to ART in cases of ART resistance and ART intolerance – 10-20% = Business opportunity $200-300 MUSD
▪ No current competition in terms of new drugs
▪ Several of the HIV leaders will begin losing market protection in 2017
▪ In 2016, four of the top 10 selling branded HIV drugs will still expand sales
▪ New international guidelines – early treatment
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Immune System Regulation Holding ABwww.israb.se
Business ModelReposition of Old Drugs for New Indications
• Cost- and Time Effective Route to Market• Out-licensing of indications beyond HIV and virus infections
Scientific ModelTo Increase Cure Rates Through Stimulation of the Immune System
• Elimination of Virus Infected Cells - Eradication
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Old Drugs Are New Again
Business Opportunity – Life Cycle Management
Drug repositioning vs typical drug development
Typical drug development Drug repositioning
Avarage cost to bring new drugs to market
USD 1.24 billion Significantly lower costs5 – 10 MUSD
Time required 10 – 17 years 3 – 12 years
Failure rates in later stages High Low
Increasing focus on Drugs to treat chronic and complex diseases
Drugs for rapidly emergingand re-emerging infectiousdiseases
Key messages; Key messages;
▪ Expensive▪ Time consuming▪ Risky
▪ To accelerate drugdevelopment
▪ Reduced risk of failure▪ Lower costs
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Repositioning of GnRH – ISR´s first drug ISR48
Drug repositioning:
Re-investigating existing drugs for new therapeutic indications
GnRH i.e. Decapeptyl Depot®;
▪ Approved indications are prostate cancer, endometriosis, pubertas preacox in children
▪ New indications; HIV, viral infections, cancer
Old Drugs Are New Again
Business Opportunity – Life Cycle Management
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Communication between The Immune and Endocrine Systems
GnRH
Stimulation of the immune system
ISR´s Lead Product a GnRH-agonistGnRH agonists as antiviral therapeutics
Feline ImmunodeficiencyVirus = Cat AIDS
In vitro/ex vivo preclinical data▪ T cells express GnRH receptors
(subtype?)▪ GnRH activates T-cells▪ GnRH upregulates class I (CD69, CD25,
CD27) on human T-cells▪ Lymphocytes from HIV patients
upregulate class I after GnRH stimulation▪ Lymphocytes from healthy donors
upregulate class I after GnRH stimulation▪ Lymphocytes from monkeys upregulate
class I after GnRH stimulation
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Phase IIb - naive HIV infected patients (ISR48)
South Africa ?China / East Asia
Phase IIa – HIV patients on ART therapy + GnRH (ISR48) Sweden (Stockholm)
Accelerate time to market of ISR48 througha parallel Phase IIa strategy
Phase IIa – Genital Herpes (ISR48)
Sweden
Objectives;▪ Confirmation of Phase
IIa results▪ Eradication of HIV
virus reservoirs▪ Treatments of virus
infections beyond HIV▪ Effects on the
immune system of ISR48 and products in pipeline
Exploratory preclinicalresearch; cancerimmunotherapy + ISR48
Out-resourced (CRO)
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ISR´s Clinical Focus
Focusing on four segments
▪ Naive HIV infection
▪ ART resistance and ART intolerance in HIV patients
▪ ART + GnRH agonist to empty HIV reservoirs
▪ Genital Herpes infection
Clinical problems
▪ ART medication in HIV patients does not eliminate the
HIV virus from cellular reservoirs
▪ There are no alternative drugs in patients with ART
resistance or ART intolerance
Clinical solutions
▪ Drugs that regulate the immune system in such a way
that the HIV virus is recognized and eliminated from
cellular reservoirs - eradication drugs
▪ A product portfolio with specific efficacy and low risk of
adverse events
▪ ISR´s focus is on products with known mechanisms of
action for severe virus diseases
ISR is in the forefront of immunotherapy and virus infections by having taken GnRH as an immune regulatory drug through Phase IIa
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The problem with ART treatment and ISR´s solution
The ART medication target the virus and its
replication machinery only – No eradication
Clinical problems with stopping ART treatment
▪ ART medication in HIV patients does not eliminate
the HIV virus from cellular reservoirs and when ART
treatment stops…………………….
▪ ….....viral load increases within 1-2 weeks leading
to AIDS
Ref; Chun et al Nature 1999
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The problem with ART treatment and ISR´s solution
ISR´s immunostimulatory medications target the immune system
Eradication strategy
Clinical solution with ISR´s first product GnRH (ISR48)
▪ When GnRH treatment stops………………..the immune system is activated…….
▪ …………viral load stays low and potentially the HIV virus is eliminated
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Product and Program Pipeline – Base Case
Program 1Clinical trialsISR48 (GnRH)
Program 2(NCEs)
Program 3(NCEs)
Program 4 and 5
ISR002 (SA) - HIV indication naive patients (drug candidate ISR48/GnRH)ISR002 (CN) – HIV indication naive patients (drug candidate ISR48/GnRH)
R&D ISR49
R&D ISR50
ISR006 - Genital Herpes (ISR48) (Herpes Simplex Type II) (ISR48)
South Africa (?) and China/AsiaPhase IIb/III pivotal (ISR002)
Sweden – Phase IIa (ISR003 + 005)
Sweden – Phase IIa (ISR006)
ISR003 - HIV indication – ART+ISR48 (eradication of HIV reservoirs) ISR005 - HIV indication – ISR48 (ART resistant patients)
New chemical entities (NCEs) ISR49
New chemical entities (NCEs) ISR50
Broad-spectrum antiviral therapies and cancer immunotherapyR&D
▪ Three independent projects in clinical development phases
▪ Potential to address a pressing medicinal need in HIV and other virus infections
▪ No pharmaceuticals registered at present for immune regulation in HIV and virus infections
▪ Strong project and patent portfolio with ample opportunity for partnerships or out licensing
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Immune System Regulation Holding AB
Organization and Partners
Advisory Board
Professor Anders SönnerborgProfessor Hans Wigzell
Partners
Regulatory Affairs
Synthetic Chemistry & Drug Development
Intellectual Property
Contract Research Organization(Clinical trial program)
R&D facilities and laboratories at Karolinska Institute
Market Manager Jihua Liu
Jihua has an M.S. in Chemical Engineering with specialization in Biology. She has
worked as scientist in University of North Carolina in USA. She has served
several years as management consultant for pharmaceutical industry. In early
2000 she started to work with business development focusing on Life Science
companies for Asian market. Jihua is mainly working with funding and investment
management of start-up and early stage biotechnology and life sciences
companies at Business Research Ltd..
CCO Lennart Dreyer
Master of Business Administration from Gothenburg University and Phd. study
Gothenburg University. Guest professor of Tsinghua University, Beijing 2003 and
honorary Dean of Wuhan International Trade University 2006. President and Dean
of IHM Business School 1993-2003. Founder of BRL in 2003 and Co-founder of
Foundation Asia Pacific Ltd (FAP). Senior consultant at Deloitte and Bain.
Chairman in the business magazine Chef for several years and member of the
board at Vigmed AB, NeuroVive Asia Inc and Vigmed China Ltd. Participated in
several start-up’s, M&A and business deals in Asia.
CEO Mikeal Brönnegård
Mikael has an MD., PhD degree from the Karolinska Institute where he still holds a
position as Associate Professor. Mikael also has several years of pharmaceutical
industry experience at both local market company and corporate level including
global business management. He has been working at an executive level in the
venture capital industry focusing on start-up and early stage investments and
business development within the biotechnology and life sciences sector. Finally,
Mikael has a broad experience from operative positions in the biotechnology
industry including a CEO position at a Nasdaq listed company Neurovive.
CSO Ola Winqvist, M.D, PhD, Professor
Professor of Cellular Immunotherapy, Head of Translational Immunology, and
Senior Consultant in Clinical Immunology at the Karolinska Institutet and
Karolinska University Hospital. The Swedish Research Council and the Swedish
Cancer Society have continuously supported Ola’s research since 1999, and he
has received various competitive grants from the European Union and Swedish
Governmental Agency for Innovation Systems for the development of
immunological therapeutics. Ola has an M.D and Ph.D. from Uppsala University in
Sweden, and did his postdoctoral research at the Scripps Research Institute in the
United States. In 2013 rewarded with the Athena Prize
Management
Board of Directors
Member of the Board Gustaaf Wolvaardt
Dr., MBChB (Pret),M.Med (Int) (Pret), FCP (SA),AMP
(Manch),PGCHE (Pret) South Africa. Dr Wolvaardt is a
medical specialist with post graduate qualifications in
management and education. He worked as a clinician and a
diplomat before founding the Foundation for Professional
Development (FPD) in 1997. FPD is one of the largest health
development organizations in Africa.
Member of the Board, Hans Glise
M.D, PhD, Professor and expert in pharmaceutical product
development and innovation-driven collaborative research.
Prior to co-founding ITH, Hans has been Vice President and
Senior Vice President at Astra Zeneca, NovoNordisk, and UCB
Chairman of the Board, Anders Milton
MD, PhD with a background as President and later CEO of the
Swedish Medical Association, Chairman of the World Medical
Association, President of the Swedish Red Cross, the Swedish
Confederation of Professional Associations (SACO), etc.
Member of boards of philanthropic foundations and for profit
companies mostly in the life science field.
Member of the Board Gunnar Jardelöw
MBA at Handelshögskolan at the University of Gothenburg
1972. Broad experience in international business, sales, and
reconstructions of companies in distress, Sales and purchase
of ships, establishing, organizing and developing international
business in different areas, such as ME, Mediterranean area,
former eastern European countries. Focus on growing
companies from local to international business.
CFO Gunnar Modalen
Gunnar has a B.A. in Finance from Lunds University and appointed Captain in the
reserve in the Royal Swedish Marines. He has over twentyfive years international
experience from senior positions in listed and unlisted companies active in areas
such as the chemicals/manufacturing industry, shipping/offshore industry,
electronic/mobile phones, gaming and international banks. Gunnar held senior
positions in the Perstorp Group during 1994-2010. Since 2010 Gunnar has been
an independent consultat upholding positions such as CFO for Rederi AB
Transatlantic (publ) and Doro AB (publ) both listed on Nasdaq Stockholm.
Gunnars latest position was Head of Investor Relations & Communication in the
gaming company Cherry AB (publ) listed on AktieTorget, Stockholm.
2017-08-23 I S R T R E A T I N G V I R A L I N F E C T I O N S T H R O U G H V I R U S E L I M I N A T I O N © 20
Immune System Regulation Holding AB
www.israb.se